Project Summary: Modern biomedical research to uncover the metabolic basis of disease is increasingly dependent on the application of complex technology. In many cases, the costs associated with the acquisition and maintenance of necessary equipment, in addition to the technical expertise needed to run these technologies, typically exceed the capabilities of individual laboratories - particularly those of investigators at the start of their careers. Hence, the overarching goal for the COBRE Molecular Mechanisms Core is to provide investigators with such technologies in the realm of functional genomics and molecular bioimaging, and thus help them to apply state of the art approaches in their research projects. The Core seeks to achieve this goal in two Specific Aims: SPECIFIC AIM 1: To provide COBRE investigators with mentoring support concerning molecular bioimaging and functional genomics technology. Application of modern biomedical technology per se does not lead to meaningful or impactful scientific progress; it requires a clear understanding of the power of specific technologies for science to emerge from data. Therefore, the Core will serve as an intellectual and advisory resource for COBRE investigators when it comes to bioimaging and functional genomics experiments, and provide mentoring so that technological approaches match up with the scientific goal of each project. Hence, the goal for this Aim is to ensure that COBRE investigators, rather than viewing technology as a perhaps unsurmountable obstacle, can in fact embrace these new technologies with confidence to further their science. SPECIFIC AIM 2: To provide COBRE investigators with direct technological support for their experiments that use molecular bioimaging and functional genomics approaches. To understand the molecular etiology that forms the pathogenic framework for disease, technologies that capture gene expression changes are of primary necessity for conducting mechanistic research, and the key technologies for the Core are three-dimensional imaging of gene expression in whole-mount tissues, and assessment of gene expression using single-cell RNA sequencing. The Core will provide COBRE investigators with turn-key access to these technologies in order to ensure that they do not get needlessly bogged down in the hands-on technical minutiae, but can fully concentrate on the science of their research projects, and on their overall productivity. Furthermore, the Core, by relying on its NIH proposal review expertise, and by ensuring that experiments meet NIH rigor and reproducibility standards and thus contribute to a strong premise, can provide the mentoring environment needed for COBRE investigators to generate competitive NIH grant proposals.